Hollow mesoporous carbon nanospheres derived from metal–organic frameworks for efficient sono-immunotherapy against pancreatic cancer

“Pancreatic cancer is a highly malignant tumor with poor treatment outcomes, as conventional therapies face challenges like low efficacy and immunosuppressive tumor microenvironment. Sono-immunotherapy, combining sonodynamic therapy with immunotherapy, is a promising approach, but efficient sono-immunotherapeutic systems are urgently needed,” explained study author Haiwei Li, from The First Affiliated Hospital of Ningbo University. The HMC nanoparticles integrate multiple advantages: a porphyrin-like structure for enhanced singlet oxygen generation, hollow mesoporous features for drug loading, and good biocompatibility for in vivo application. “This integrated nano-platform provides a novel strategy for pancreatic cancer treatment, improving therapeutic efficacy while reducing potential side effects,” said the study authors. Thus, they developed HMC nanoparticles via calcination-etching with SiO₂@ZIF-8 as the sacrificial template, which can synergize with ultrasound and PD-L1 inhibitors to achieve efficient sono-immunotherapy

MOF-derived carbon materials have gained attention for their unique structures and excellent performance in biomedicine. The preparation of HMC nanoparticles involves simple and scalable processes: SiO₂@ZIF-8 composite synthesis, high-temperature calcination, and ammonia etching to remove the SiO₂ template. “3D structure control and functional modification of MOF-derived carbon materials are key to their biomedical application, and our HMC nanoparticles with hollow mesoporous structure can both mediate sonodynamic therapy and load small-molecule drugs,” said Libin Chen, the study’s first author.

The study authors showed that HMC nanoparticles exhibit superior singlet oxygen generation capacity compared to commercial TiO₂. In vitro experiments confirmed that HMC can enter tumor cells, generate reactive oxygen species (ROS) under ultrasound, induce mitochondrial membrane potential reduction and apoptosis, and promote the release of immune factors like HMGB1 and CRT to activate dendritic cells. In vivo tests demonstrated that HMC combined with ultrasound and PD-L1 inhibitor significantly inhibits tumor growth in both transplanted and in situ pancreatic cancer models, with good biocompatibility and no obvious damage to major organs.

“Our HMC nanoparticles effectively overcome the limitations of traditional pancreatic cancer therapy by disrupting the immunosuppressive microenvironment and enhancing immune cell accumulation in tumors. Nevertheless, there are still areas for improvement: the pore structure regularity of HMC needs optimization, and the long-term in vivo safety and pharmacokinetic profiles require further investigation. In addition, the combination with other therapeutic modalities such as chemotherapy or radiotherapy deserves exploration to achieve better synergistic effects,” said Shengmin Zhang from The First Affiliated Hospital of Ningbo University. Overall, this HMC-based sono-immunotherapeutic strategy is innovative and feasible, offering a new direction for the clinical treatment of pancreatic cancer.

Authors of the paper include Libin Chen, Haiwei Li, Jing Liu, Yunzhong Wang, and Shengmin Zhang.

The authors acknowledge funding from the Ningbo Natural Science Foundation (2022J221) and the Zhejiang Province Medical and Health Science and Technology Project (2024KY1502).

The paper, “Hollow Mesoporous Carbon Nanospheres Derived from Metal–Organic Frameworks for Efficient Sono-immunotherapy against Pancreatic Cancer” was published in the journal Cyborg and Bionic Systems on May 9, 2025, at DOI: 10.34133/cbsystems.0247.